tbuckley/cabot-search huggingface dataset:
Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report
Authors: Noah G Schwartz, Alfonso C Hernandez-Romieu, Pallavi Annambhotla, Thomas D Filardo, Sandy P Althomsons, Rebecca J Free, Ruoran Li, W Wyatt Wilson, Molly Deutsch-Feldman, Marci Drees, Emily Hanlin, Kelly White, Kimberly A Lehman, Tyler C Thacker, Scott A Brubaker, Brychan Clark, Sridhar V Basavaraju, Isaac Benowitz, Janet Burton Glowicz, Lauren S Cowan, Angela M Starks, Sapna Bamrah Morris, Philip LoBue, Rebekah J Stewart, Jonathan M Wortham, Maryam B Haddad
Journal: The Lancet Infectious Diseases (2022)
Transmission of HIV Possibly Associated With Exposure of Mucous Membrane to Contaminated Blood
Journal: JAMA (1997)

In February 1996, transmission of human immunodeficiency virus (HIV) by an unknown route involving an HIV-infected man and his previously uninfected female sex partner was reported to CDC. This report summarizes the epidemiologic investigation of this transmission, which suggests that the woman was infected through mucous membrane exposure to contaminated blood.
Ultrabright nanoparticle-labeled lateral flow immunoassay for detection of anti-SARS-CoV-2 neutralizing antibodies in human serum
Authors: Lun Bian, Zhaoyue Li, An He, Biru Wu, Hui Yang, Yingsong Wu, Fang Hu, Guanfeng Lin, Deqing Zhang
Journal: Biomaterials (2022)
Administration of Zidovudine During Late Pregnancy and Delivery to Prevent Perinatal HIV Transmission--Thailand, 1996-1998
Journal: JAMA (1998)

Worldwide, approximately 500,000 infants are perinatally infected with human immunodeficiency virus (HIV) each year, most of whom are born in developing countries. In 1994, a clinical trial in the United States and France demonstrated that zidovudine (ZDV) administered orally five times a day to HIV-infected pregnant women starting at 14-34 weeks' gestation, intravenously during labor, and orally to their newborns for 6 weeks reduced the risk for perinatal HIV transmission by two thirds. In 1994, this regimen was recommended as standard care in the United States; however, because of its complexity and cost, this regimen has not been implemented in most developing countries, and no other intervention had been efficacious in reducing perinatal HIV transmission. In 1996, the Ministry of Public Health of Thailand and Mahidol University, in collaboration with CDC, initiated a randomized, placebo-controlled trial of a simpler and less expensive regimen of ZDV to prevent perinatal HIV transmission. This report describes preliminary trial results, which indicate that a short-term antenatal regimen of ZDV reduced the risk for perinatal HIV transmission by approximately half.
Covid-19: What we know about the BA.4 and BA.5 omicron variants
Authors: Elisabeth Mahase
Journal: BMJ (2022)

Covid-19: What we know about the BA.4 and BA.5 omicron variants Two omicron subvariants have come to dominate infections worldwide.Elisabeth Mahase summarises what we know about them so far Elisabeth MahaseWhen and where were these subvariants detected?BA.4 and BA.5 were first detected in South Africa in January and February 2022, respectively. 1They are offshoots of the omicron variant BA.2, though their additional mutations seem to have given them a transmission advantage. 2What's the difference between BA.4 and BA.5?The World Health Organization has said that BA.5 now accounts for more than half of the world's cases, while BA.4 accounts for just over one in 10. 3 Why BA.5 has overtaken BA.4 is a mystery, because they're so similar.Speaking at a Royal Society of Medicine event, Thomas Peacock, a virologist at Imperial College London, said, "They have identical spikes, more or less.So that means it has to be something outside the spike.And really our understanding of that from a virological perspective is very poor.
False-negative and false-positive outcomes of computer-aided detection on brain metastasis: Secondary analysis of a multicenter, multireader study
Authors: Xiao Luo, Yadi Yang, Shaohan Yin, Hui Li, Weijing Zhang, Guixiao Xu, Weixiong Fan, Dechun Zheng, Jianpeng Li, Dinggang Shen, Yaozong Gao, Ying Shao, Xiaohua Ban, Jing Li, Shanshan Lian, Cheng Zhang, Lidi Ma, Cuiping Lin, Yingwei Luo, Fan Zhou, Shiyuan Wang, Ying Sun, Rong Zhang, Chuanmiao Xie
Journal: Neuro-Oncology (2022)

Abstract Background Errors have seldom been evaluated in computer-aided detection on brain metastases. This study aimed to analyze false negatives (FNs) and false positives (FPs) generated by a brain metastasis detection system (BMDS) and by readers. Methods A deep learning-based BMDS was developed and prospectively validated in a multicenter, multireader study. Ad hoc secondary analysis was restricted to the prospective participants (148 with 1,066 brain metastases and 152 normal controls). Three trainees and 3 experienced radiologists read the MRI images without and with the BMDS. The number of FNs and FPs per patient, jackknife alternative free-response receiver operating characteristic figure of merit (FOM), and lesion features associated with FNs were analyzed for the BMDS and readers using binary logistic regression. Results The FNs, FPs, and the FOM of the stand-alone BMDS were 0.49, 0.38, and 0.97, respectively. Compared with independent reading, BMDS-assisted reading generated 79% fewer FNs (1.98 vs 0.42, P &amp;lt; .001); 41% more FPs (0.17 vs 0.24, P &amp;lt; .001) but 125% more FPs for trainees (P &amp;lt; .001); and higher FOM (0.87 vs 0.98, P &amp;lt; .001). Lesions with small size, greater number, irregular shape, lower signal intensity, and located on nonbrain surface were associated with FNs for readers. Small, irregular, and necrotic lesions were more frequently found in FNs for BMDS. The FPs mainly resulted from small blood vessels for the BMDS and the readers. Conclusions Despite the improvement in detection performance, attention should be paid to FPs and small lesions with lower enhancement for radiologists, especially for less-experienced radiologists.
CD8 T cells contribute to vaccine protection against SARS-CoV-2 in macaques
Authors: Jinyan Liu, Jingyou Yu, Katherine McMahan, Catherine Jacob-Dolan, Xuan He, Victoria Giffin, Cindy Wu, Michaela Sciacca, Olivia Powers, Felix Nampanya, Jessica Miller, Michelle Lifton, David Hope, Kevin Hall, Nicole P. Hachmann, Benjamin Chung, Tochi Anioke, Wenjun Li, Jeanne Muench, Adrienne Gamblin, Mona Boursiquot, Anthony Cook, Mark G. Lewis, Hanne Andersen, Dan H. Barouch
Journal: Science Immunology (2022)

Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recently, robust vaccine prevention of severe disease with SARS-CoV-2 variants that largely escape NAb responses has been reported, suggesting a role for other immune parameters for virologic control. However, direct data demonstrating a role of CD8+ T cells in vaccine protection have not yet been reported. In this study, we show that vaccine-elicited CD8+ T cells contribute substantially to virologic control after SARS-CoV-2 challenge in rhesus macaques. We vaccinated 30 macaques with a single immunization of the adenovirus vector-based vaccine Ad26.COV2.S or sham and then challenged them with 5 × 105 median tissue culture infectious dose SARS-CoV-2 B.1.617.2 (Delta) by the intranasal and intratracheal routes. All vaccinated animals were infected by this high-dose challenge but showed rapid virologic control in nasal swabs and bronchoalveolar lavage by day 4 after challenge. However, administration of an anti-CD8α- or anti-CD8β-depleting monoclonal antibody in vaccinated animals before SARS-CoV-2 challenge resulted in higher levels of peak and day 4 virus in both the upper and lower respiratory tracts. These data demonstrate that CD8+ T cells contribute substantially to vaccine protection against SARS-CoV-2 replication in macaques.
<i>Vital Signs:</i> Hepatitis C Treatment Among Insured Adults — United States, 2019–2020
Authors: William W. Thompson, Hasan Symum, Amy Sandul, Neil Gupta, Priti Patel, Noele Nelson, Jonathan Mermin, Carolyn Wester
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Over 2 million adults in the United States have hepatitis C virus (HCV) infection, and it contributes to approximately 14,000 deaths a year. Eight to 12 weeks of highly effective direct-acting antiviral (DAA) treatment, which can cure ≥95% of cases, is recommended for persons with hepatitis C.Data from HealthVerity, an administrative claims and encounters database, were used to construct a cohort of adults aged 18-69 years with HCV infection diagnosed during January 30, 2019-October 31, 2020, who were continuously enrolled in insurance for ≥60 days before and ≥360 days after diagnosis (47,687). Multivariable logistic regression was used to assess the association between initiation of DAA treatment and sex, age, race, payor, and Medicaid restriction status; adjusted odds ratios (aORs) and 95% CIs were calculated.The prevalence of DAA treatment initiation within 360 days of the first positive HCV RNA test result among Medicaid, Medicare, and private insurance recipients was 23%, 28%, and 35%, respectively; among those treated, 75%, 77%, and 84%, respectively, initiated treatment within 180 days of diagnosis. Adjusted odds of treatment initiation were lower among those with Medicaid (aOR = 0.54; 95% CI = 0.51-0.57) and Medicare (aOR = 0.62; 95% CI = 0.56-0.68) than among those with private insurance. After adjusting for insurance type, treatment initiation was lowest among adults aged 18-29 and 30-39 years with Medicaid or private insurance, compared with those aged 50-59 years. Among Medicaid recipients, lower odds of treatment initiation were found among persons in states with Medicaid treatment restrictions (aOR = 0.77; 95% CI = 0.74-0.81) than among those in states without restrictions, and among persons whose race was coded as Black or African American (Black) (aOR = 0.93; 95% CI = 0.88-0.99) or other race (aOR = 0.73; 95% CI = 0.62-0.88) than those whose race was coded as White.Few insured persons with diagnosed hepatitis C receive timely DAA treatment, and disparities in treatment exist. Unrestricted access to timely DAA treatment is critical to reducing viral hepatitis-related mortality, disparities, and transmission. Treatment saves lives, prevents transmission, and is cost saving.
Validation of Proposed Criteria for Progressive Pulmonary Fibrosis
Authors: Janelle Vu Pugashetti, Ayodeji Adegunsoye, Zhe Wu, Cathryn T. Lee, Anand Srikrishnan, Sahand Ghodrati, Vivian Vo, Elisabetta A. Renzoni, Athol U. Wells, Christine Kim Garcia, Felix Chua, Chad A. Newton, Philip L. Molyneaux, Justin M. Oldham
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Criteria for progressive pulmonary fibrosis (PPF) have been proposed, but their prognostic value beyond categorical decline in FVC remains unclear. Objectives: To determine whether proposed PPF criteria predict transplant-free survival (TFS) in patients with non–idiopathic pulmonary fibrosis (IPF) forms of interstitial lung disease (ILD). Methods: A retrospective, multicenter cohort analysis was performed. Patients with diagnoses of fibrotic connective tissue disease–associated ILD, fibrotic hypersensitivity pneumonitis, and non-IPF idiopathic interstitial pneumonia from three U.S. centers and one UK center constituted the test and validation cohorts, respectively. Cox proportional hazards regression was used to test the association between 5-year TFS and ⩾10% FVC decline, followed by 13 additional PPF criteria satisfied in the absence of ⩾10% FVC decline. Measurements and Main Results: One thousand three hundred forty-one patients met the inclusion criteria. A ⩾10% relative FVC decline was the strongest predictor of reduced TFS and showed consistent TFS association across cohorts, ILD subtypes, and treatment groups, resulting in a phenotype that closely resembled IPF. Ten additional PPF criteria satisfied in the absence of 10% relative FVC decline were also associated with reduced TFS in the U.S. test cohort, with 6 maintaining TFS associations in the UK validation cohort. Validated PPF criteria requiring a combination of physiologic, radiologic, and symptomatic worsening performed similarly to their stand-alone components but captured a smaller number of patients. Conclusions: An FVC decline of ⩾10% and six additional PPF criteria satisfied in the absence of such decline identify patients with non-IPF ILD at increased risk for death or lung transplantation.
Impaired renal reserve contributes to preeclampsia via the kynurenine and soluble fms–like tyrosine kinase 1 pathway
Authors: Vincent Dupont, Anders H. Berg, Michifumi Yamashita, Chengqun Huang, Ambart E. Covarrubias, Shafat Ali, Aleksandr Stotland, Jennifer E. Van Eyk, Belinda Jim, Ravi Thadhani, S. Ananth Karumanchi
Journal: Journal of Clinical Investigation (2022)

To understand how kidney donation leads to an increased risk of preeclampsia, we studied pregnant outbred mice with prior uninephrectomy and compared them with sham-operated littermates carrying both kidneys. During pregnancy, uninephrectomized (UNx) mice failed to achieve a physiological increase in the glomerular filtration rate and during late gestation developed hypertension, albuminuria, glomerular endothelial damage, and excess placental production of soluble fms-like tyrosine kinase 1 (sFLT1), an antiangiogenic protein implicated in the pathogenesis of preeclampsia. Maternal hypertension in UNx mice was associated with low plasma volumes, an increased rate of fetal resorption, impaired spiral artery remodeling, and placental ischemia. To evaluate potential mechanisms, we studied plasma metabolite changes using mass spectrometry and noted that l-kynurenine, a metabolite of l-tryptophan, was upregulated approximately 3-fold during pregnancy when compared with prepregnant concentrations in the same animals, consistent with prior reports suggesting a protective role for l-kynurenine in placental health. However, UNx mice failed to show upregulation of l-kynurenine during pregnancy; furthermore, when UNx mice were fed l-kynurenine in drinking water throughout pregnancy, their preeclampsia-like state was rescued, including a reversal of placental ischemia and normalization of sFLT1 levels. In aggregate, we provide a mechanistic basis for how impaired renal reserve and the resulting failure to upregulate l-kynurenine during pregnancy can lead to impaired placentation, placental hypoperfusion, an antiangiogenic state, and subsequent preeclampsia.
Durvalumab After Sequential Chemoradiotherapy in Stage III, Unresectable NSCLC: The Phase 2 PACIFIC-6 Trial
Authors: Marina C. Garassino, Julien Mazieres, Martin Reck, Christos Chouaid, Helge Bischoff, Niels Reinmuth, Laura Cove-Smith, Talal Mansy, Diego Cortinovis, Maria R. Migliorino, Angelo Delmonte, José Garcia Sánchez, Luis Enrique Chara Velarde, Reyes Bernabe, Luis Paz-Ares, Ignacio Diaz Perez, Nataliya Trunova, Kayhan Foroutanpour, Corinne Faivre-Finn
Journal: Journal of Thoracic Oncology (2022)

IntroductionOn the basis of the findings of the phase 3 PACIFIC trial (NCT02125461), durvalumab is standard of care for patients with stage III, unresectable NSCLC and no disease progression after concurrent chemoradiotherapy (cCRT). Many patients are considered unsuitable for cCRT owing to concerns with tolerability. The phase 2 PACIFIC-6 trial (NCT03693300) evaluates the safety and tolerability of durvalumab after sequential CRT (sCRT).MethodsPatients with stage III, unresectable NSCLC and no progression after platinum-based sCRT were enrolled to receive durvalumab (1500 mg intravenously) every 4 weeks for up to 24 months. The primary end point was the incidence of grade 3 or 4 adverse events possibly related to treatment occurring within 6 months. Secondary end points included investigator-assessed progression-free survival (PFS; Response Evaluation Criteria in Solid Tumors version 1.1) and overall survival.ResultsOverall, 117 patients were enrolled (59.8% with performance status >0, 65.8% aged ≥65 y, and 37.6% with stage IIIA disease). Median treatment duration was 32.0 weeks; 37.6% of patients remained on treatment at data cutoff (July 15, 2021). Grade 3 or 4 AEs occurred in 18.8% of patients. Five patients had grade 3 or 4 possibly related adverse events within 6 months (incidence: 4.3%; 95% confidence interval: 1.4–9.7), including two pneumonitis cases. Two patients (1.7%) had grade 5 AEs of any cause. Survival data maturity was limited. Median PFS was 10.9 months (95% confidence interval: 7.3–15.6), and 12-month PFS and overall survival rates were 49.6% and 84.1%, respectively.ConclusionsDurvalumab after sCRT had a comparable safety profile with that observed with durvalumab after cCRT in PACIFIC and had encouraging preliminary efficacy in a frailer population.
NVX-CoV2373 vaccination induces functional SARS-CoV-2–specific CD4+ and CD8+ T cell responses
Authors: Carolyn Rydyznski Moderbacher, Christina Kim, Jose Mateus, Joyce Plested, Mingzhu Zhu, Shane Cloney-Clark, Daniela Weiskopf, Alessandro Sette, Louis Fries, Gregory Glenn, Shane Crotty
Journal: Journal of Clinical Investigation (2022)

NVX-CoV2373 is an adjuvanted recombinant full-length SARS-CoV-2 spike trimer protein vaccine demonstrated to be protective against COVID-19 in efficacy trials. Here we demonstrate that vaccinated individuals made CD4+ T cell responses after 1 and 2 doses of NVX-CoV2373, and a subset of individuals made CD8+ T cell responses. Characterization of the vaccine-elicited CD8+ T cells demonstrated IFN-γ production. Characterization of the vaccine-elicited CD4+ T cells revealed both circulating T follicular helper (cTfh) cells and Th1 cells (IFN-γ+, TNF-α+, and IL-2+) were detectable within 7 days of the primary immunization. Spike-specific CD4+ T cells were correlated with the magnitude of the later SARS-CoV-2-neutralizing antibody titers, indicating that robust generation of CD4+ T cells, capable of supporting humoral immune responses, may be a key characteristic of NVX-CoV2373 that utilizes Matrix-M adjuvant.
Schaftoside inhibits 3CLpro and PLpro of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19
Authors: Yang Yi, Meng Zhang, Heng Xue, Rong Yu, Yang-Oujie Bao, Yi Kuang, Yue Chai, Wen Ma, Jing Wang, Xiaomeng Shi, Wenzhe Li, Wei Hong, Junhua Li, Elishiba Muturi, Hongping Wei, Joachim Wlodarz, Szczepan Roszak, Xue Qiao, Hang Yang, Min Ye
Journal: Acta Pharmaceutica Sinica B (2022)

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro and PLpro with IC50 values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC50 of 11.83 ± 3.23 μmol/L. Hydrogen–deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.
D–A Type NIR‐II Organic Molecules: Strategies for the Enhancement Fluorescence Brightness and Applications in NIR‐II Fluorescence Imaging‐Navigated Photothermal Therapy
Authors: Yan Chen, Shangyu Chen, Haoli Yu, Yuesong Wang, Mengyuan Cui, Peng Wang, Pengfei Sun, Min Ji
Journal: Advanced Healthcare Materials (2022)

NIR-II fluorescence imaging (NIR-II FI) and photothermal therapy (PTT) have received broad attentions in precise tumor diagnosis and effective treatment attributed to high-resolution and deep tissue imaging, negligible invasivity, and high-efficiency treatment. Although many fluorescent molecules have been designed and conducted for NIR-II FI and PTT, it is still an enormous challenge for researchers to pioneer some rational design guidelines to improve fluorescence brightness. Organic D-A-type molecules, including small molecules and conjugated polymers, can be designed and developed to improve fluorescence brightness due to their tunable and easy functionalized chemical structures, allowing molecules tailored photophysical properties. In this review, some approaches to the development and design strategies of D-A type small molecules and conjugated polymers for the enhancement of fluorescence brightness are systemically introduced. Meanwhile, some applications of PTT and PTT-based combination therapy (such as PDT, chemotherapy, or gas therapy) assisted by NIR-II FI-based single or multiimaging technologies are classified and represented in detail as well. Finally, the current issues and challenges of NIR-II organic molecules in NIR-II FI-navigated PTT are summarized and discussed, which gives some guidelines for the future development direction of NIR-II organic molecules for NIR-II FI-navigated PTT.
Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response
Authors: S Loibl, A Schneeweiss, J Huober, M Braun, J Rey, J-U Blohmer, J Furlanetto, D-M Zahm, C Hanusch, J Thomalla, C Jackisch, P Staib, T Link, K Rhiem, C Solbach, P A Fasching, V Nekljudova, C Denkert, M Untch
Journal: Annals of Oncology (2022)
Raman studies of the adipose tissue: Current state-of-art and future perspectives in diagnostics
Authors: Krzysztof Czamara, Zuzanna Majka, Ewa Stanek, Natalia Hachlica, Agnieszka Kaczor
Journal: Progress in Lipid Research (2022)

The last decades revealed that the adipose tissue shows an unexplored therapeutic potential. In particular, targeting the perivascular adipose tissue (PVAT), that surrounds blood vessels, can prevent cardiovascular pathologies and browning of the adipose tissue can become an effective strategy against obesity. Therefore, new analytical tools are necessary to analyze this tissue. This review reports on the recent developments of various Raman-based techniques for the identification and quantification of the adipose tissue compared to conventional analytical methods. In particular, the emphasis is on analysis of PVAT, investigation of pathological changes of the adipose tissue in model systems and possibilities for its characterization in the clinical context. Overall, the review critically discusses the potential and limitations of Raman techniques in adipose tissue-targeted diagnostics and possible future anti-obesity therapies.